Liver transplantation is a lifesaving procedure with excellent outcomes for patients with fulminant liver failure and end-stage liver disease. Advances in surgical techniques, postoperative care, and immunosuppression have led to marked improvements in both graft and patient survival over time. However, biliary complications after surgery remain a key cause of morbidity and mortality among liver transplant recipients, affecting approximately 5% to 35% [1]. Common biliary complications include anastomotic and nonanastomotic biliary strictures, bile leaks, and bilomas. Bile duct stones and casts are also observed in a minority of patients [2]. The incidence of biliary strictures is reported to be between 5% and 25%, with a higher occurrence in cases of living donor liver transplantation (LDLT) compared to deceased donor liver transplantation (DDLT) [1,3]. Several factors contribute to the greater incidence of strictures in LDLT, including smaller bile ducts, multiple and relatively proximal anastomoses, and the risk of bile duct devascularization due to hilar dissection. Biliary strictures typically present within the first 6 to 12 months after transplantation, although presentations on either side of this timeframe are not uncommon [4,5]. These strictures are primarily classified as anastomotic or nonanastomotic. Early anastomotic strictures may be caused by size mismatches between donor and recipient ducts and local edema, while late anastomotic strictures often occur due to ischemic fibrosis. Nonanastomotic strictures result from diffuse ischemic injuries to the bile ducts, which can be due to antibody-mediated rejection, hepatic artery thrombosis (HAT), chronic ductopenic rejection, and ABO-incompatible (ABOi) liver transplant [3,6].

Endoscopic therapy is regarded as the primary therapy for the management of posttransplant biliary strictures. Percutaneous and surgical approaches are required when endoscopic retrograde cholangiopancreatography (ERCP) is contraindicated or unsuccessful [7,8]. Limited evidence is available concerning the prevalence and long-term outcomes of biliary strictures in LDLT. The present study aimed to examine the incidence and characteristics of biliary strictures in LDLT recipients, along with their impact on long-term graft and patient survival.

In this retrospective observational study, we analyzed data from a prospectively collected database at Max Super Specialty Hospital in New Delhi, India, a tertiary care facility where over 400 LDLT procedures are performed annually. The study received approval from the relevant Institutional Ethics Committee (TM/MSSH/MHIL/ISC/LIVER & BILIARY SCIENCES/23-72). In accordance with the institutional protocol for retrospective observational studies, the requirement for participant consent was waived.

The study included adult LDLT recipients who underwent surgery between 2006 and 2022. We collected relevant clinical information, including demographic details, blood biochemistry findings, radiological imaging, indications for liver transplantation, preoperative prognostic scores such as the Child-Turcotte-Pugh (CTP) score and the Model For End-Stage Liver Disease (MELD), surgical details, types of vascular and biliary anastomosis, and liver allograft characteristics, including weight, graft-to-recipient weight ratio, and ischemia time. The exclusion criteria included an age under 18 years and a pretransplant diagnosis of primary sclerosing cholangitis (PSC) or PSC overlap syndrome. Additionally, patients who received ABOi allografts and those who underwent retransplantation were excluded from the study.

All recipients and donors provided written informed consent for surgery following a detailed explanation of the planned procedure. The liver transplant program at our institute adheres strictly to the 2008 Declaration of Istanbul on organ transplantation. All donors were at least 18 years old and were biologically related to their respective recipients. Donor selection at our center is governed by a rigorous stepwise process that includes a preoperative clinical assessment conducted by a hepatologist, transplant surgeon, psychiatrist, and anesthetist. The laboratory assessment encompasses liver function tests, complete blood count, kidney function tests, viral serologies, and other biochemical analyses. For donors, imaging includes computed tomography (CT) volumetry, CT angiography, and magnetic resonance cholangiopancreatography (MRCP). Liver biopsy is selectively performed in candidates with deranged liver function tests and high potential for a steatotic graft.

A total of 3,550 patients underwent liver transplantation between August 2006 and December 2022. After excluding pediatric cases, deceased donor transplants, PSC, PSC overlap, ABOi transplants, and retransplantations, 2,956 adult recipients were analyzed for biliary complications. Of these, 209 (7.1%) experienced bile leak in the early postoperative period. Among the patients with biliary leaks, 51 (24.4%) experienced in-hospital mortality, 54 (25.8%) developed biliary strictures, and 104 (49.7%) did not develop strictures during follow-up. Of the 2,747 patients without biliary leak in the immediate postoperative period, 296 (10.7%) died in the hospital, 290 (10.5%) developed biliary strictures, and 2,161 (78.6%) did not develop strictures. Patients who developed biliary strictures, whether after biliary leak or not, were categorized into the stricture group. Those who did not develop biliary stricture, regardless of whether it followed biliary leak, were placed in the no-stricture group (Fig. 1).

During the study period, biliary strictures were observed in 344 cases, accounting for 11.6% of the total. The median age of patients with strictures was significantly higher than that of those without strictures (50 vs. 49 years, P=0.044). Additionally, median MELD (21 vs. 18, P<0.001) and CTP scores (11 vs. 10, P=0.0008) were significantly higher in the stricture group. The proportions of diabetes mellitus and hypertension were also significantly higher among recipients with strictures. In both groups, the liver donors were predominantly male. Donors in the stricture group exhibited a significantly higher median age (32 vs. 30 years, P=0.011). Graft weight, graft-to-recipient weight ratios, and ischemic times did not differ significantly between the two groups. The use of extended right lobes was significantly less common in the stricture group (6.1% vs. 11.2%, P=0.038). Most patients in the study underwent duct-to-duct biliary anastomosis, and the type of biliary anastomosis was similar between groups. However, the mean number of anastomoses was significantly higher among those with strictures, at 1.3 versus 1.2 (P<0.001) (Tables 1 and 2).

The rates of postoperative complications such as bleeding (3.8% vs. 1.2%, P<0.001) and bile leak (15.7% vs. 4.6%, P<0.001) were significantly higher among patients with strictures. Other complications, including HAT, middle hepatic vein obstruction, and portal vein thrombosis, were comparable between the two groups. Additionally, the median duration of stay in the intensive care unit (14 vs. 10 days, P<0.001) and the overall hospital stay (26 vs. 21 days, P<0.001) were significantly longer in the stricture group.

Over a median follow-up period of 11 months (interquartile range, 5–24 months), nearly four-fifths of the patients with strictures, specifically 265 (77.0%), underwent ERCP as the primary modality to alleviate this condition (Fig. 2). PTBD was the primary therapy for 73 patients (21.2%). ERCP was successful in 175 (66.0%) of the cases, with a mean of 1.89 sessions per patient. Cholangitis was the most common ERCP-related complication, occurring in 20 patients (7.6%). Post-ERCP pancreatitis developed in seven patients (2.7%), and two patients experienced ERCP-related perforation. Fourteen patients (15.9%) with failed ERCP underwent hepaticojejunostomy. In contrast, only one patient who initially received PTBD was treated with hepaticojejunostomy (Fig. 2).

In this retrospective study, the overall rate of biliary stricture in adult recipients of LDLT was 11.45%. ERCP served as the first-line treatment for most of these patients and was successful in approximately 66% of cases. The median time for the development of strictures was 11 months posttransplant. Cholangitis was the most common complication following ERCP, occurring in 7.6% of cases, while post-ERCP pancreatitis was observed in 2.7%. The 1-year and 3-year survival rates for patients with biliary strictures were 94.1% and 84.9%, respectively.

Patients treated with LDLT have a higher incidence of biliary strictures compared to those receiving organs from deceased donors, for several reasons. In LDLT, the graft ducts tend to be smaller, and multiple anastomoses may be present since the biliary anastomosis is often more proximal. Additionally, devascularization of the bile duct due to hilar dissection and injuries at the cut surface of the bile duct contribute to the increased risk [2,8–10]. There is a scarcity of large-scale studies on biliary complications in LDLT recipients [1,2,8]. Wadhawan et al. [8] previously reported on biliary outcomes after liver transplant in 338 patients, noting a biliary stricture rate of 13.3%. More recently, Gad et al. [11] identified a 22% incidence of biliary strictures [11]. Other studies have indicated a stricture rate ranging from 15% to 25% among LDLT recipients [2,12–14]. The overall biliary stricture rate in our study was 11.6%, which is low relative to most published studies. Over time, advancements in surgical techniques have led to a reduced rate of biliary strictures at our center. A combination of refined surgical procedures, the surgeons’ accumulated experience, and other factors likely contributed to the lower incidence of biliary strictures. Our institute represents one of the largest LDLT centers in India and Asia, with decades of experience and surgical expertise.

In addition to bile leak, our study revealed that advanced donor and recipient age, higher MELD score, and multiple biliary anastomoses were associated with an increased risk of biliary strictures in liver transplant recipients. Previous studies have reported these factors as contributing to the risk of anastomotic biliary strictures after LDLT. Wadhawan et al. [8] demonstrated that the presence of multiple biliary anastomoses was a risk factor for posttransplant biliary strictures. In another study by Akamatsu et al. [2], bile leak and living donor status were identified as risk factors for biliary strictures. Other research has indicated that a high MELD score, prolonged cold and warm ischemia times, advanced donor and recipient age, and conventional biliary anastomosis are risk factors for biliary stricture in liver transplant recipients [2]. The surgical technique used for biliary anastomosis can also influence the rate of biliary complications. Duct-to-duct anastomosis may be performed using continuous absorbable sutures, interrupted nonabsorbable sutures, or a mixed technique. However, previous studies have not demonstrated any significant difference in outcomes with different techniques [15–17]. At our center, biliary anastomosis is typically performed in a duct-to-duct manner when feasible, using 7-0 PDS sutures. Prior to 2023, the posterior layer was completed continuously, while the anterior layer was done in an interrupted fashion. However, since 2023, both layers have been established using an interrupted technique.

Minimally invasive donor hepatic resection in LDLT, including both laparoscopic and robotic techniques, provides better cosmetic outcomes and facilitates the early recovery of living donors. However, the adoption of these methods is not yet widespread, and research on their long-term outcomes is limited. In the present study, minimally invasive donor surgery was not identified as a risk factor for biliary strictures in liver transplant recipients. Song et al. [18] reported on 295 patients who underwent laparoscopic donor hepatectomy, demonstrating outcomes comparable to those of open donor surgery [18–21]. Notably, only a small number of patients in our study underwent minimally invasive surgery, and more robust evidence from larger studies is required.

In a recent study by Taniai et al. [22], ABO incompatibility was the only identified risk factor for biliary strictures. However, the study had a small sample size, including only 26 patients. ABOi liver transplantation is recognized as a risk factor for nonanastomotic diffuse biliary strictures [22]. Nonanastomotic strictures were not observed in our study, as we excluded patients with ABOi liver transplantation and PSC. The exclusion of these patients may have contributed to the lower overall incidence of biliary stricture in our study.

ERCP remains the primary modality of choice for the management of biliary strictures. In LDLT, the success rate of ERCP has been reported to be low compared to DDLT and other forms of benign strictures. Various studies have reported success rates for ERCP in these patients ranging from 40% to 92%. Differences in the definition of ERCP success and variations in technical expertise may account for these disparate results. Akamatsu et al. [2] reported a success rate of 57% in a systematic review [23–25]. In our study, ERCP was successful in 66% of cases, and cholangitis (7.6%) and pancreatitis (2.7%) were the two most frequent complications observed. The reported incidence rates of pancreatitis and cholangitis in liver transplant recipients range from 2.7% to 6.4% and 0.7% to 5.1%, respectively [26–28]. Less common complications include bleeding and perforation, which occurred in 0.8% and 0.4% of cases, respectively, in our study. The use of preprocedural antibiotics and the reduction of immunosuppression during the periprocedural period can help lower the risk of infectious complications. Most patients with nonresolution of strictures following ERCP were successfully managed with a percutaneous approach, and hepaticojejunostomy was performed in selected cases.

Overall, patient and graft survival rates in individuals with biliary strictures were comparable to those in patients without biliary strictures. However, the median hospital stay was longer for patients with biliary strictures, as they experienced a higher incidence of bile leak during the postoperative period.

Bile leak is a major risk factor for the development of biliary strictures. In our study, the incidence of bile leak was 7%; previous studies have reported rates of 2% to 25% [2,6]. Most of our patients improved with conservative treatment alone. Endoscopic intervention was reserved for patients with persistent bile leak beyond 4 to 6 weeks after liver transplantation. Bile leak and strictures largely share reported risk factors, including advanced donor and recipient age, higher CTP score, higher MELD score, prolonged cold and warm ischemia times, and HAT. The presence of smaller and multiple bile ducts may also elevate the risk of bile leak. Additionally, the incidence of bile leak can be influenced by the surgical techniques used for biliary anastomosis reconstruction [1,17,29–32]. In our study, higher MELD score, multiple biliary anastomoses, and the use of hepaticojejunostomy for biliary reconstruction were identified as risk factors for bile leak. Another notable finding from our study was that only 34.1% of patients with bile leak developed biliary strictures. Although bile leak is a known and common cause of biliary stricture, its presence does not invariably lead to stricture formation. Many patients with bile leak who received conservative management recovered without any delayed biliary complications.

Our study has several limitations. Most notably, it was retrospective in nature and exclusively included recipients of LDLT. Consequently, the results may not be generalizable to DDLT recipients. Nevertheless, this study represents one of the largest investigations into the incidence and predictors of biliary strictures among LDLT recipients, with a sample of over 2,500 patients.

In conclusion, anastomotic biliary strictures and bile leaks significantly contribute to morbidity in liver transplant recipients. With advancements in surgical techniques, the incidence rate of these biliary complications has significantly decreased. Although postoperative biliary strictures contribute to considerable morbidity, they do not affect patient survival. Effective endoscopic and nonendoscopic treatment modalities are available to manage these complications.